For the therapy of chronic diseases (rheumatoid arthritis and autoimmune diseases) with which the immune response is concerned, anti-inflammatory agents, immunomodulators, etc. are used. The formers are for symptomatic therapy, thus cannot become fundamental therapeutic agents. Whereas, the latters, in which gold salt and D-penicillamine, levamisole, lobenzarit, etc. are known, have attracted an attention for the last several years.
The inventors have also studied diligently for the purpose of developing a more effective and safer anti-rheumatic agent and have found previously that the cyclic anthranilic acid derivatives have immunomodulatory action and inducing ability for suppressor T cells, and that they have therapeutic effect against rheumatoid arthritis (Japanese Unexamined Patent Publication No. Hei 1-279867). However in cyclic aminophenylacetic acid derivatives, compounds having such action are not known.
In cyclic aminophenylacetic acid derivatives having different substituent from the compounds in this invention, those having anti-inflammatory, antipyretic and analgesic actions are described in Japanese Unexamined Patent Publication No. Sho 58-116466 and U.S. Pat. No. 3,778,511 (1973), but the immuno-modulating action is not referred at all. These publicly known compounds, with which a possibility to cause gastrointestinal injury is suggested, belong to a category of non-steroidal anti-inflammatory drugs having cyclooxygenase-inhibitory action, and their usefulness is not satisfactory from the points of efficacy and toxicity. Moreover, cyclic aminophenylacetic acid derivatives exhibiting monoamineoxydase-inhibitory action are also known (Chemical Abstract, Vol. 64, 1753c (1966), ibid Vol. 70, 10292f(1969)), but these also differ from the compounds of the invention in the structure and action.